The effect of walking on regional blood flow and acetylcholine in the hippocampus in conscious rats

Recent studies in our laboratory have demonstrated that stimulation of the septal complex (i.e., the medial septal nucleus and the nucleus of the diagonal band) increases extracellular acetylcholine (ACh) release and, consequently, results in an increase in regional cerebral blood flow in the hippocampus (Hpc CBF) via activation of the nicotinic ACh receptors (nAChRs) [Neurosci. Lett. 107 (1989) 135; Neurosci. Lett. 112 (1990a) 263]. The present study aimed to examine the effects of walking on Hpc CBF, measured by laser Doppler flowmetry, in conscious rats. Walking at a moderate speed (4 cm/s) on a treadmill for 30 s produced increases in Hpc CBF and mean arterial pressure (MAP), reaching 107+/-1% and 105 +/-1% of the prewalking control values, respectively. Walking for 3 min produced an increase in ACh release in the extracellular space of the hippocampus. The increase in Hpc CBF during walking was attenuated by mecamylamine (abbreviated as MEC here; 2 mg/kg, i.v.), a nAChR antagonist permeable to the blood-brain barrier (131313), but not by hexamethonium (denoted as C6 here; 20 mg/kg, i.v.), a nAChR antagonist impermeable to the BBB, while the walking-induced increase in MAP was abolished by either agent. The response of Hpc CBF and MAP were not altered by atropine (abbreviated as ATR here; 0.5 mg/kg, i.v.), a muscarinic AChR antagonist permeable to the BBB. The increase in Hpc CBF during walking was attenuated by N-omega-nitro-L-arginine methyl ester (L-NAME, 3 and 30 mg/kg, i.v.), a nitric oxide synthase, (NOS) inhibitor, and the reduced responses were reversed following the intravenous (i.v.) administration of a physiological precursor of NO, L-arginine (600 mg/kg). The results suggest that the increase in Hpc CBF during walking is independent of MAP and attributable at least to activation of the nAChRs by the cholinergic vasodilator nerves projecting to the hippocampus and to production of NO in the hippocampus. (C) 2002 Elsevier Science B.V. All rights reserved.